Non-transmissible MV Vector with Segmented RNA Genome Establishes Different Types of iPSCs from Hematopoietic Cells

Mol Ther. 2020 Jan 8;28(1):129-141. doi: 10.1016/j.ymthe.2019.09.007. Epub 2019 Sep 12.

Abstract

Recent advances in gene therapy technologies have enabled the treatment of congenital disorders and cancers and facilitated the development of innovative methods, including induced pluripotent stem cell (iPSC) production and genome editing. We recently developed a novel non-transmissible and non-integrating measles virus (MV) vector capable of transferring multiple genes simultaneously into a wide range of cells through the CD46 and CD150 receptors. The MV vector expresses four genes for iPSC generation and the GFP gene for a period of time sufficient to establish iPSCs from human fibroblasts as well as peripheral blood T cells. The transgenes were expressed differentially depending on their gene order in the vector. Human hematopoietic stem/progenitor cells were directly and efficiently reprogrammed to naive-like cells that could proliferate and differentiate into primed iPSCs by the same method used to establish primed iPSCs from other cell types. The novel MV vector has several advantages for establishing iPSCs and potential future applications in gene therapy.

Keywords: RNA virus; hematopoietic stem cell; iPSC; measles virus; naïve; non-integrating; non-transmissible; segmented RNA genome; vector; viral gene transfer vector.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Donors
  • Cell Differentiation / genetics
  • Cellular Reprogramming / genetics*
  • Fibroblasts / metabolism
  • Genetic Therapy / methods
  • Genetic Vectors*
  • Genome, Viral / genetics*
  • HEK293 Cells
  • Hematopoietic Stem Cells / metabolism*
  • Heterografts
  • Humans
  • Induced Pluripotent Stem Cells / metabolism*
  • Male
  • Measles virus / genetics*
  • Mice
  • Mice, Inbred NOD
  • RNA, Viral / genetics*
  • Sendai virus / genetics
  • T-Lymphocytes / metabolism
  • Transduction, Genetic
  • Transgenes

Substances

  • RNA, Viral